Alpha-Adrenergic receptors mediate multiple regulatory functions including vasoconstriction and feedback inhibition of norepinephrine release. Renal vascular resistance and reactivity leading to vasoconstriction are increased in hypertensive man and rats and may be an initiating factor in systemic hypertension. We have preliminary evidence of increased alpha-adrenergic receptor number in the Okamoto strain of spontaneously hypertensive rats. This abnormality is accompanied, in young hypertensive rats, with elevated plasma norepinephrine levels suggesting a failure of suppression of receptor synthesis in this genetic strain. Such an alteration in alpha-receptors could mediate the increased renal resistance or reactivity and conceivably the high blood pressure in these animals. We are thus proposing to extend these preliminary studies in other hypertensive models and into man, to attempt altering the receptor number pharmacologically and to do appropriate in vivo and in vitro correlative studies to establish the significance of this biochemical abnormality. Additionally, we are proposing to extend our preliminary findings in conscious rats which suggest alpha-receptor selectivity of the alpha blocking agent prazosin into man and to further characterize this selectivity in animals.